QL706 + Chemo ± Bevacizumab in Anti-PD-(L)1-Resistant R/M Cervical Cancer

Official title

A Prospective, Open-Label, Single-Arm Study of Iparomlimab and Toripalimab Plus Nab-Paclitaxel With or Without Bevacizumab in Recurrent/Metastatic Cervical Cancer Progressed on Anti-PD-(L)1 Therapy

Overview

This is a clinical research study for women with recurrent or metastatic cervical cancer whose disease has progressed after prior treatment with a PD-1/PD-L1 inhibitor immunotherapy. The study will evaluate the effectiveness and safety of a new combination treatment consisting of iparvolimab and tuvonralimab (QL1706)-a dual-targeting immunotherapy drug-along with chemotherapy (nab-paclitaxel) with or without bevacizumab, an anti-angiogenic drug that may help prevent tumor growth. Approximately 25 participants will be enrolled in this open-label, single-arm study. All participants will receive the study treatment for up to 6 cycles, followed by maintenance therapy until disease progression, unacceptable side effects, or other reasons for stopping treatment. The main goal of the study is to see how many patients respond to the treatment (Objective Response Rate, ORR). Other goals include measuring how long the response lasts, how long patients live without the cancer getting worse, and overall survival. Safety and quality of life will also be closely monitored. This study is for women aged 18-75 who have previously received PD-1/PD-L1 treatment and whose cancer has worsened. Participants must be in generally good health with adequate organ function and no other active cancers. The study will be conducted at a single center in China. All participants will provide written informed consent before joining the study.

Detailed description

This is a prospective, open-label, single-arm, single-center phase II clinical trial investigating the efficacy and safety of a combination therapy in patients with recurrent or metastatic cervical cancer who have experienced disease progression following prior anti-PD-1/PD-L1 therapy.

The study aims to address the high unmet medical need in this patient population where treatment options are limited after failure of immunotherapy. The investigational regimen consists of iparomlimab and tuvonralimab (QL1706), a novel bifunctional antibody targeting both PD-1 and CTLA-4, combined with nab-paclitaxel chemotherapy, with the optional addition of bevacizumab at the investigator's discretion.

Approximately 25 participants will receive the combination treatment for 6 cycles (3-week cycles), followed by maintenance therapy with QL1706 ± bevacizumab until disease progression, unacceptable toxicity, or other discontinuation criteria are met. The primary endpoint is Objective Response Rate (ORR) per RECIST 1.1. Secondary endpoints include Progression-Free Survival (PFS), Duration of Response (DoR), Disease Control Rate (DCR), Overall Survival (OS), and safety profile. An exploratory objective will analyze the correlation between PD-L1 expression status and treatment outcomes.

The study will include rigorous safety monitoring per NCI CTCAE v5.0 guidelines and regular tumor assessments. The sample size was calculated based on the assumption of improving the ORR from a historical control of 15% to 40% with the new combination.

Interventions

• Biological Iparomlimab and Tuvonralimab (QL1706) + Nab-Paclitaxelwith or without Bevacizumab
  All participants will receive the study intervention: Iparomlimab and Tuvonralimab (QL1706) at 5.0 mg/kg IV Q3W + Nab-Paclitaxel at 260 mg/m² IV Q3W, with or without Bevacizumab (7.5-15 mg/kg IV Q3W) per investigator's choice, for 6 cycles. This is followed by maintenance therapy with QL1706 ± Bevacizumab until disease progression, unacceptable toxicity, or other discontinuation criteria are met.

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: From enrollment until disease progression, unacceptable toxicity, or any other discontinuation criterion is met (assessed approximately every 8 weeks for up to 24 months)]

Secondary outcome measures (4)

• Progression-Free Survival (PFS) [Time frame: From enrollment until disease progression or death (assessed approximately every 8 weeks for up to 24 months).]
• Duration of Response (DoR) [Time frame: From the first recorded response until disease progression or death (assessed approximately every 8 weeks for up to 24 months).]
• Disease Control Rate (DCR) [Time frame: From enrollment until disease progression, unacceptable toxicity, or any other discontinuation criterion is met (assessed approximately every 8 weeks for up to 24 months).]
• Overall Survival (OS) [Time frame: From enrollment until death from any cause (assessed every 12 weeks during follow-up for up to 24 months).]

Eligibility criteria

Inclusion criteria

• Female patients aged 18 to 75 years.
• Histologically, pathologically, or radiologically confirmed recurrent or metastatic cervical cancer.
• At least one measurable lesion as defined by RECIST 1.1 (non-nodal lesion longest diameter ≥10 mm or lymph node short axis ≥15 mm).
• ECOG performance status of 0 or 1.
• Life expectancy ≥12 weeks.
• Disease progression after receiving at least one prior anti-PD-1/PD-L1 monoclonal antibody therapy (alone or in combination).
• Adequate organ function within 14 days before enrollment:

Absolute neutrophil count (ANC) >1.5 × 10⁹/L Platelets >100 × 10⁹/L Hemoglobin >100 g/L Serum total bilirubin <1.5 × ULN ALT and AST <3 × ULN Creatinine clearance (CCr) >60 mL/min

• Voluntarily sign the informed consent form, able to understand and comply with study requirements.

Exclusion criteria

• Known allergy to any component of the study drugs.
• Prior treatment with any CTLA-4 targeting medication.
• Adverse reactions from previous anti-cancer therapy have not recovered to ≤ Grade 1 (per CTCAE v5.0) (except for toxicities without safety risk per investigator's judgment, e.g., alopecia).
• History of other malignancies within the past 5 years, except for cured malignancies.
• Severe comorbid conditions, including but not limited to:

Extensive interstitial lung disease requiring medication. Active or uncontrolled infections (e.g., tuberculosis, HIV). Decompensated liver disease, active hepatitis, or active bleeding. History of cerebrovascular accident or pulmonary embolism. Active, known, or suspected autoimmune diseases. Active infection requiring systemic anti-infective therapy.

• Ascites with depth >5 cm measured by ultrasound or CT, OR ascites causing severe symptoms (e.g., abdominal distension, dyspnea, circulatory dysfunction) significantly impacting physical function or study safety.
• Pregnant, planning pregnancy, or lactating women.
• Any other condition deemed by the investigator as unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07186868 · NCC-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗